rs6560891

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_170682.4(P2RX2):c.636-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,613,580 control chromosomes in the GnomAD database, including 304,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34539 hom., cov: 33)

Exomes 𝑓: 0.61 ( 270352 hom. )

Consequence

P2RX2
NM_170682.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.521

Publications

21 publications found

Variant links:

Genes affected

P2RX2 (HGNC:15459): (purinergic receptor P2X 2) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Aug 2013]

P2RX2 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 41
Inheritance: AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

P2RX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-132620432-G-A is Benign according to our data. Variant chr12-132620432-G-A is described in ClinVar as Benign. ClinVar VariationId is 226986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4 link	c.636-13G>A		intron_variant	Intron 6 of 10	ENST00000643471.2	NP_733782.1	Q9UBL9-1Q32MC3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2 link	c.636-13G>A		intron_variant	Intron 6 of 10		NM_170682.4	ENSP00000494644.1		Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.666

AC:

101185

AN:

151976

Hom.:

34505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.733

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.803

Gnomad SAS

AF:

0.606

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.637

GnomAD2 exomes

AF:

0.643

AC:

161399

AN:

251172

AF XY:

0.629

show subpopulations

Gnomad AFR exome

AF:

0.799

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.508

Gnomad EAS exome

AF:

0.812

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.605

AC:

884394

AN:

1461486

Hom.:

270352

Cov.:

AF XY:

0.603

AC XY:

438748

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.797

AC:

26674

AN:

33478

American (AMR)

AF:

0.784

AC:

35077

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

13243

AN:

26130

East Asian (EAS)

AF:

0.805

AC:

31953

AN:

39700

South Asian (SAS)

AF:

0.594

AC:

51198

AN:

86248

European-Finnish (FIN)

AF:

0.558

AC:

29753

AN:

53288

Middle Eastern (MID)

AF:

0.602

AC:

3470

AN:

5766

European-Non Finnish (NFE)

AF:

0.590

AC:

656144

AN:

1111774

Other (OTH)

AF:

0.611

AC:

36882

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

19485

38970

58456

77941

97426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18126

36252

54378

72504

90630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.666

AC:

101273

AN:

152094

Hom.:

34539

Cov.:

AF XY:

0.665

AC XY:

49480

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.799

AC:

33147

AN:

41506

American (AMR)

AF:

0.734

AC:

11224

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1754

AN:

3470

East Asian (EAS)

AF:

0.803

AC:

4148

AN:

5164

South Asian (SAS)

AF:

0.606

AC:

2922

AN:

4820

European-Finnish (FIN)

AF:

0.560

AC:

5926

AN:

10588

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.590

AC:

40099

AN:

67930

Other (OTH)

AF:

0.640

AC:

1353

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1693

3386

5079

6772

8465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.623

Hom.:

72579

Bravo

AF:

0.685

Asia WGS

AF:

0.692

AC:

2404

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

636-13G>A in intron 6 of P2RX2: This variant is not expected to have clinical si gnificance because it has been identified in 41.4% (3564/8600) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs6560891). -

Autosomal dominant nonsyndromic hearing loss 41

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.7

(source)

DANN

Benign

0.88

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over